Selective androgen receptor modulators (SARMs) are a class of drugs that selectively activate the androgen receptor in certain tissues like muscle and bone over other tissues like the prostate gland and seminal vesicles.
Andarine is a selective androgen receptor modulator (SARM) which was developed by GTX, Inc for the treatment of conditions such as muscle wasting, osteoporosis, and benign prostatic hypertrophy (BPH), using the nonsteroidal antiandrogen bicalutamide as a lead compound. Development of andarine for all indications has been discontinued, in favor of the structurally related and improved compound enobosarm.
Selective glucocorticoid receptor modulators (SEGRMs) and selective glucocorticoid receptor agonists (SEGRAs) formerly known as dissociated glucocorticoid receptor agonists (DIGRAs) are a class of experimental drugs designed to share many of the desirable anti-inflammatory, immunosuppressive, or anticancer properties of classical glucocorticoid drugs but with fewer side effects such as skin atrophy. Although preclinical evidence on SEGRAMs’ anti-inflammatory effects are culminating, currently, the efficacy of these SEGRAMs on cancer are largely unknown.
LGD-3303 is a drug which acts as a selective androgen receptor modulator (SARM), with good oral bioavailability. It is a selective agonist for the androgen receptor, producing functional selectivity with effective dissociation of anabolic and androgenic effects, acting as a partial agonist for androgenic effects, but a full agonist for anabolic effects. It has been investigated as a possible treatment for osteoporosis, and was shown in animal studies to enhance the effectiveness of a bisphosphonate drug.
Prinaberel is a synthetic, nonsteroidal, and highly selective agonist of the ERβ subtype of the estrogen receptor. It is used in scientific research to elucidate the role of the ERβ receptor. Studies have indicated that selective ERβ agonists like prinaberel could be useful in the clinical treatment of a variety of medical conditions including inflammatory bowel disease, rheumatoid arthritis, endometriosis, and sepsis. Accordingly, prinaberel either was or still is under investigation by Wyeth for the treatment of some of these conditions.
Samidorphan is an opioid antagonist that in the form of olanzapine/samidorphan is used in the treatment of schizophrenia and bipolar disorder. Samidorphan reduces the weight gain associated with olanzapine. Samidorphan is taken by mouth.
AZD-5423 is a nonsteroidal glucocorticoid and phase II experimental drug being developed by AstraZeneca and disclosed at the spring 2013 American Chemical Society meeting in New Orleans to treat respiratory diseases and in particular chronic obstructive pulmonary disease.
Ligandrol, also known by the developmental code names VK5211 and LGD-4033, is a selective androgen receptor modulator (SARM) which is under development for the treatment of muscle atrophy in people with hip fracture. It was also under development for the treatment of cachexia, hypogonadism, and osteoporosis, but development for these indications was discontinued. Ligandrol has been reported to dose-dependently improve lean body mass and muscle strength in preliminary clinical trials, but is still being developed and has not been approved for medical use. The drug is taken by mouth.
Vosilasarm, also known by the development codes RAD140 and EP0062 and by the black-market name Testolone or Testalone, is a selective androgen receptor modulator (SARM) which is under development for the treatment of hormone-sensitive breast cancer. It is specifically under development for the treatment of androgen receptor-positive, estrogen receptor-negative, HER2-negative advanced breast cancer. Vosilasarm was also previously under development for the treatment of sarcopenia, osteoporosis, and weight loss due to cancer cachexia, but development for these indications was discontinued. The drug is taken by mouth.
MK-0773, also known as PF-05314882, is a steroidal, orally active selective androgen receptor modulator (SARM) that was under development by Merck and GTx for the treatment of sarcopenia in women and men. Clinical trials for sarcopenia began in late 2007 but the collaboration between Merck and GTx ended in early 2010 and GTx terminated development of MK-0773 shortly thereafter. MK-0773 was developed as a more advanced version of the related compound TFM-4AS-1.
WAY-214156 is a synthetic nonsteroidal estrogen that acts as a highly selective agonist of the ERβ. It is 100-fold selective for the ERβ over the ERα with an IC50 of 4.2 nM (compare to estradiol with IC50 values of ~3–4 nM for both the ERα and ERβ). The drug is less selective for the ERβ than is prinaberel (ERB-041, WAY-202041), another selective ERβ agonist, but is more potent in comparison. WAY-214156 may produce anti-inflammatory effects via the ERβ and has been proposed as a potential treatment for inflammatory conditions such as rheumatoid arthritis.
Fosdagrocorat is a nonsteroidal but steroid-like selective glucocorticoid receptor modulator (SGRM) which was under development for the treatment of rheumatoid arthritis but was never marketed. It is the C2 dihydrogen phosphate ester of dagrocorat, and acts as a prodrug of dagrocorat with improved pharmacokinetics. The drug reached phase II clinical trials prior to the discontinuation of its development.
Relacorilant is an antiglucocorticoid which is under development by Corcept Therapeutics for the treatment of Cushing's syndrome. It is also under development for the treatment of solid tumors and alcoholism. The drug is a nonsteroidal compound and acts as an antagonist of the glucocorticoid receptor. As of December 2017, it is in phase II clinical trials for Cushing's syndrome and phase I/II clinical studies for solid tumors, while the clinical phase for alcoholism is unknown.
BMS-641988 is a nonsteroidal antiandrogen which was developed by Bristol-Myers Squibb for the treatment of prostate cancer but was never marketed. It acts as a potent competitive antagonist of the androgen receptor (AR) (Ki = 10 nM; IC50Tooltip half-maximal inhibitory concentration = 56 nM). The drug was found to have 20-fold higher affinity for the AR than bicalutamide in MDA-MB-453 cells, and showed 3- to 7-fold the antiandrogenic activity of bicalutamide in vitro. It may have some weak partial agonist activity at the androgen receptor. BMS-641988 is transformed by CYP3A4 into BMS-570511, and this metabolite is then reduced to BMS-501949 by cytosolic reductases. All three compounds show similar antiandrogenic activity. In addition to its antiandrogenic activity, BMS-641988 shows activity as a negative allosteric modulator of the GABAA receptor, and can produce seizures in animals at sufficiently high doses. It also shows some drug-induced QT prolongation. BMS-641988 reached phase I clinical trials prior to the discontinuation of its development. The clinical development of BMS-641988 was terminated due to the occurrence of a seizure in a patient during a phase I study.
EM-5854 is a steroidal antiandrogen which was under development by Endoceutics, Inc. for the treatment of prostate cancer. It was first described in a patent in 2008, and was further characterized in 2012. EM-5854 reached phase I/II clinical trials for the treatment of prostate cancer but development was discontinued in March 2019.
β-LGND2, also known as ERβ-selective ligand 2 or as GTx-878, is a synthetic nonsteroidal estrogen and selective ERβ agonist which was under development by GTx for the treatment of benign prostatic hyperplasia, prostatitis, and rheumatoid arthritis but was never marketed. It shows approximately 25-fold selectivity for activation of the ERβ over the ERα (EC50Tooltip half-maximal effective concentration = 2 nM and 52 nM, respectively). β-LGND2 is an isoquinolinone derivative.
WAY-204688, also known as SIM-688, is a synthetic nonsteroidal estrogen and nuclear factor κB (NF-κB) inhibitor which was originated by ArQule and Wyeth and was under development by Wyeth for the treatment of rheumatoid arthritis, non-specific inflammation, and sepsis but was never marketed. It is a "pathway-selective" estrogen receptor (ER) ligand which inhibits NF-κB with an IC50Tooltip half-maximal inhibitory concentration of 122 nM and with maximal inhibition relative to estradiol of 94%. Inhibition of NF-κB by WAY-204688 appears to be dependent on agonism of the ERα, as it is reversed by the ERα antagonist fulvestrant, but is not dependent on the ERβ. In contrast to the case of NF-κB inhibition, WAY-204688 produces only slight elevation of creatine kinase in vitro, a measure of classical estradiol effects. It reached phase I clinical trials prior to the discontinuation of its development.
